It’s unclear whether the anti-NGF causes damage and if so, why. One theory is that the pain medication is so effective that people tend to be more active and overuse their damaged joints. “The individual is not able to sense traumatic damage like small fractures due to a lack of sensation, and therefore keeps using the joint, adding to the damage, until it is an end-stage joint requiring joint replacement,” Dr. Nelson explains.

Another possibility is that anti-NGFs affect the blood supply to the joint. “The idea regarding blood supply is that NGF also has a role in the process of angiogenesis, or new blood vessel formation, and somehow by blocking NGF, there is a loss of blood flow to the joint, leading to bone death,” Dr. Nelson says.

At the hearing, each drug company presented an analysis of its study data conducted by its own internal and independent experts. Though their research was at different stages, all the drug makers agree the problems were likely connected to the size of the dose as well as combining the anti-NGFs with NSAIDs.

According to documents submitted by Pfizer to the FDA, “Withdrawals [from the trials] due to adverse events generally increased as a function of the tanezumab dose administered (2.5, 5, or 10 mg) and at any given dose of tanezumab, the addition of an NSAID further increased the incidence of discontinuation due to adverse events.”

All three companies recommended restarting drug trials with the anti-NGFs alone, not in patients also taking NSAIDs. They also proposed limiting the dose and excluding patients with advanced OA.

Nancy E. Lane, MD, a professor of medicine and rheumatology at the University of California, Davis, was one of the authors of the study in NEJM that tested Pfizer’s tanezumab. She applauds the panel’s recommendation to continue with the research.

“The early stages show it can be quite effective, and I think if it’s shown to be safe in additional studies that it will be a useful medication to treat pain for our patients,” she said after the hearing.

Dr. Nelson says it’s good to be cautious about this new class of drug given the seriousness of these complications. But she also believes new treatments for OA pain are badly needed for the roughly 27 million Americans living with the condition. Current pain-control options can be problematic. Long-term use of NSAIDs, like aspirin and ibuprofen, can cause gastrointestinal bleeding and are contraindicated for many patients; opioid analgesics have a long list of side effects, including risk of dependence; and acetaminophen at the recommended doses is often not strong enough.  

“For those people who don’t have other options, [anti-NGFs are] very promising. As a rheumatologist, I see a lot of those folks in my clinic,” Dr. Nelson says. “They can’t have a joint replacement. They can’t tolerate NSAIDs and the other things we have to offer now. In those folks, I think, this has a high degree of promise for alleviating pain and improving quality of life, if the way to use it safely can be identified.”

It isn’t known when – or if – anti-NGFs would become available to the public. At this point, Dr. Nelson says, “The best evidence is still really for weight management, exercise, dietary changes, a healthy lifestyle and those types of interventions. The lifestyle elements are still where most of the evidence is, and are the best things that people can do.”